USP7 Inhibition Clears Up to Half of Irradiation Induced Senescent Cells From Mouse Tissues

Researchers here report on the discovery of a novel mechanism by which senescent cells can be selectively destroyed. Short-term senolytic treatments to date seem to cluster tightly into two categories: (a) largely ineffective, and (b) able to destroy between 25-50% of senescent cells in tissues. Few have achieved greater clearance so far, and few lie in between these two outcomes. In the present environment, of ample seed stage funding and enthusiasm for targeting senescent cells as a treatment for aging, it seems likely that someone will pick up this new approach for clinical development in the near future. Although cellular senescence is an important tumor-suppressive mechanism, emerging evidence demonstrates that the accumulation of senescent cells (SnCs) with age and after genotoxic or cytotoxic cancer therapy can lead to various age-related diseases and pathological conditions. The selective removal of SnCs depends on identifying their Achilles' heels, which can be targeted to selectively kill SnCs. Several senolytic targets have been identified, resulting in the discovery of a series of senolytic agents that can selectively kill SnCs in culture and effectively remove SnCs in mice. Unfortunately, some of these agents exhibit toxicities that may prevent their safe use in the clinic, particularly for systemic therapy. For example, navitoclax, a selective BCL-2/BCL-XL dual inhibitor, is a potent senolytic agent but can induce thrombocytopenia, an on-target and dose...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs

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In conclusion, the recently demonstrated protective effects of NMN treatment on neurovascular function can be attributed to multifaceted sirtuin-mediated anti-aging changes in the neurovascular transcriptome. Our present findings taken together with the results of recent studies using mitochondria-targeted interventions suggest that mitochondrial rejuvenation is a critical mechanism to restore neurovascular health and improve cerebral blood flow in aging. Wnt/β-Catenin Signaling as a Point of Intervention to Spur Greater Neural Regeneration https://www.fightaging.org/archives/2020/02/wnt-%ce%b2-catenin-sig...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
This study shows that CA are released from periventricular and subpial regions to the cerebrospinal fluid and are present in the cervical lymph nodes, into which cerebrospinal fluid drains through the meningeal lymphatic system. We also show that CA can be phagocytosed by macrophages. We conclude that CA can act as containers that remove waste products from the brain and may be involved in a mechanism that cleans the brain. Moreover, we postulate that CA may contribute in some autoimmune brain diseases, exporting brain substances that interact with the immune system, and hypothesize that CA may contain brain markers that m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
We present a contemporary analysis of risk of fatal stroke among more than 7.5 million cancer patients and report that stroke risk varies as a function of disease site, age, gender, marital status, and time after diagnosis. The risk of stroke among cancer patients is two times that of the general population and rises with longer follow-up time. The relative risk of fatal stroke, versus the general population, is highest in those with cancers of the brain and gastrointestinal tract. The plurality of strokes occurs in patients older than 40 years of age with cancers of the prostate, breast, and colorectum. Patients of any ag...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
Discussion MDSCs violently emerge in pathological conditions in an attempt to limit potentially harmful immune and inflammatory responses. Mechanisms supporting their expansion and survival are deeply investigated in cancer, in the perspective to reactivate specific antitumor responses and prevent their contribution to disease evolution. These findings will likely contribute to improve the targeting of MDSCs in anticancer immunotherapies, either alone or in combination with immune checkpoint inhibitors. New evidence indicates that the expansion of myeloid cell differentiation in pathology is subject to fine-tuning, as its...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusions This review describes how leukocyte-heparanase can be a double-edged sword in tumor progression; it can enhance tumor immune surveillance and tumor cell clearance, but also promote tumor survival and growth. We also discuss the potential of using heparanase in leukocyte therapies against tumors, and the effects of heparanase inhibitors on tumor progression and immunity. We are just beginning to understand the influence of heparanase on a pro/anti-tumor immune response, and there are still many questions to answer. How do the pro/anti-tumorigenic effects of heparanase differ across different cancer types? Does...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In conclusion, MPT0G413 and BTZ synergistically inhibit MM viability, providing a framework for the clinical evaluation of combined therapies for MM. Introduction Multiple myeloma (MM) is a B cell malignancy characterized by the proliferation of bone marrow (BM) plasma cells and the production of large amounts of abnormal immunoglobulins (1) In the United States, it was estimated that 30,770 new MM cases would be diagnosed in 2018, accounting for 1.8% of newly diagnosed cancer cases (2). Furthermore, 12,770 MM-related deaths in 2018 accounted for an estimated 2.1% of all cancer deaths (2). In the past decade, MM t...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Authors: Mkhitaryan S, Danielyan S, Sargsyan L, Hakobyan L, Iskanyan S, Bardakchyan S, Papyan R, Arakelyan J, Sahakyan K, Avagyan T, Tananyan A, Muradyan A, Tamamyan G Abstract Background: Chemotherapy-induced thrombocytopenia (CIT) is a significant complication of cancer therapy. Data on the optimal management approaches of this morbidity in children and young adults are still limited. Aim: The aim of the study is to estimate the frequency and severity of CIT and associated clinically significant bleeding in children and young adults with solid tumours and haematologic malignancies. Methods: For this retro...
Source: Ecancermedicalscience - Category: Cancer & Oncology Tags: Ecancermedicalscience Source Type: research
Thrombocytopenia is a frequent complication of cancer may be due to a variety of causes including malignancy itself, acute disease processes, or cancer therapy. Systemic cancer therapy is the most common cause of thrombocytopenia in cancer patients observed nearly two-thirds of patients with solid tumors. Thrombocytopenia with traditional chemotherapy agents is most frequently the result of megakaryocyte cytotoxicity. Oxaliplatin is a platinum derivative commonly used in gastrointestinal malignancies and is associated with drug-induced immune thrombocytopenia.Case Rep Oncol 2018;11:880 –882
Source: Case Reports in Oncology - Category: Cancer & Oncology Source Type: research
The evasion of apoptosis, or programmed cell death, is a hallmark of cancer, which promotes tumor initiation and progression. The evasion is in part attributable to the over-expression of anti-apoptotic proteins in the Bcl-2 family. In addition, chemotherapy and radiation can upregulate the expression of the Bcl-2 family in cancer cells, which renders them more resistance to cancer therapy. The most common Bcl-2 family member over-expressed in many solid tumor cells and a fraction of leukemia and lymphoma cells is Bcl-XL and its expression is also highly correlated with resistance to cancer therapy independent of p53 statu...
Source: Blood - Category: Hematology Authors: Tags: 614. Acute Lymphoblastic Leukemia: Therapy, excluding Transplantation: Poster II Source Type: research
This study demonstrated that the hematologic toxicity of S‐1 regimen was the lowest, while Gemcitabine regimen exhibited the lowest incidence rate of non‐hematologic toxicity, providing guidance for the treatment of advanced/metastatic PC. This article is protected by copyright. All rights reserved
Source: Journal of Cellular Biochemistry - Category: Biochemistry Authors: Tags: Article Source Type: research
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